tbuckley/cabot-search huggingface dataset:
Sulfotransferase-Mediated Chlorination of 1-Hydroxymethylpyrene to a Mutagen Capable of Penetrating Indicator Cells
Authors: Hansruedi Glatt, Reinhard Henschler, David H. Phillips, Jerry W. Blake, Pablo Steinberg, Albrecht Seidel, Franz Oesch
Journal: Environmental Health Perspectives (1990)

Methylated polycyclic aromatic hydrocarbons are common in the human environment. Many of them are stronger carcinogens than their purely aromatic congeners. They may be metabolized to benzylic alcohols. We report here on biochemical and toxicological characteristics of 1-hydroxymethylpyrene (HMP), a typical representative of this class of compounds. Rat liver cytosol, fortified with 3'-phosphoadenosine-5'-phosphosulfate, converted HMP into its sulfate ester (HMPS), HMPS bound covalently to isolated DNA. In physiological buffer at 37 degrees C, HMPS had a half-life of 2 min, the major decomposition product being HMP. Thus, cyclic activation is possible. When Cl- anions were present at physiological concentrations, an additional reaction product of HMPS, 1-chloromethylpyrene (ClMP), could be identified on the basis of its chromatographic properties and its mass spectrum, using the authentic standard for comparison. ClMP was shorter-lived in buffer than HMPS. ClMP reacted with DNA, the adduct pattern in the 32P-postlabeling analysis being similar, or identical, to that of HMPS. ClMP proved to be a very potent mutagen in Salmonella typhimurium, whereas HMPS, and HMP in the presence of a sulfate-conjugating system, showed strong mutagenicity only when Cl- or Br- ions were present in the exposure buffer. It is concluded that HMPS is capable of reacting with DNA, but is hampered in its distribution by membrane barriers.(ABSTRACT TRUNCATED AT 250 WORDS)
Will Supersonic Airliners Create Medical Problems?
Journal: JAMA (1966)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Instructions to Authors
Journal: Circulation Research (1974)

Circulation Research accepts for publication manuscripts that present the results of significant research on the cardiovascular and the renal systems.First priority is given to unpublished research that provides better understanding of mechanisms that influence normal or abnormal cardiovascular-renal function.The research may be in the field of biology, biochemistry, biophysics, clinical medicine, genetics, immunology, morphology, pathology, pharmacology, physiology, or theoretic biology -or it may be interdisciplinary.Lower priority is given to reports that merely confirm published work, that present a new method or a modification of an existing method without applying it to a biologic problem, or that are preliminary or incomplete.Since the number of papers that can be published each year is limited, only manuscripts that receive a relatively high priority can be accepted for publication.
Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma
Authors: Fred Hochberg, Stuart A. Grossman, Tom Mikkelsen, Michael Glantz, Joy D. Fisher, Steven Piantadosi
Journal: Neuro-Oncology (2000)

9-Aminocamptothecin (9-AC) was administered as a 72-h i.v.infusion every 2 weeks to a total of 99 adults with high-grade astrocytomas.Fifty-one patients with newly diagnosed glioblastoma multiforme received 9-AC treatment prior to radiation therapy and 48 patients with highgrade astrocytomas were treated at the time of tumor recurrence.Upon entrance into these research protocols, all patients had measurable disease that was evaluated on a monthly basis with volumetric CT or MRI scans.A partial response was de ned by 50% reduction in the contrast enhancing volume on stable or decreasing doses of glucocorticoids.The study speci ed that all apparent responders would have central review of their radiologic studies and histopathology.The initial patients treated with 9-AC were also receiving anticonvulsants and were noted to have minimal myelosuppression with this chemotherapy.Thus, 9-AC doses were escalated from the previously reported maximum tolerated dose (MTD) of 850 µg/m 2 /24 h.We then established new MTDs for patients receiving enzyme-inducing anticonvulsants.We de ned these MTDs to be 1776 µg/m 2 /24 h for newly diagnosed, previously untreated patients and 1611 µg/m 2 /24 h for patients with recurrent disease.Twentytwo patients with newly diagnosed glioblastoma multiforme received 9-AC at doses 1776 µg/m 2 /24 h.Of these, 18 had evaluable disease on central review, and 0 of 18 (0%) demonstrated a partial or complete response.Twenty-one patients with recurrent high-grade astrocytomas were treated at 1611 µg/m 2 /24 h; 20 had evaluable disease and 0 of 20 (0%) had a partial or complete response.Thus, the overall response rate in the 38 evaluable patients treated at the MTD was 0 of 38 (0%).Furthermore, of the 51 evaluable patients who were treated at doses less than the MTD, only one partial response was observed, yielding an overall response rate of 2%.Evidence of drug failure was rapid with tumor progression in one-half of patients after 2 drug cycles.9-AC lacks evidence of substantial activity in patients with newly diagnosed or recurrent high-grade astrocytomas.
NATIVE DRUG PLANTS OF THE UNITED STATES.
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Long-term responders to sunitinib therapy for metastatic renal cell carcinoma (mRCC).
Authors: A. M. Molina, X. Jia, M. S. Ginsberg, S. Velasco, D. R. Feldman, S. Patil, R. J. Motzer
Journal: Journal of Clinical Oncology (2010)

4610 Background: Sunitinib has established efficacy in mRCC pts (NEJM 2007; 356:115). We report long-term responders, defined as patients (pts) achieving ongoing complete response (CR) or remaining progression-free for ≥ 18 months on sunitinib. Methods: From 1/03-3/06, 139 pts were treated with sunitinib alone (64 pts) or in combination (75 pts) on 7 clinical trials at MSKCC. Median progression-free survival (PFS) was 11 mos (95% CI 8-15); median OS was 24 mos (95% CI 18-34). 24 of the 139 were identified as long-term responders. Results: Characteristics for the 24 and the entire cohort of 139 were examined (Table). Best response was CR in 3, partial response in 19, and stable disease in 2 pts. Median duration of sunitinib therapy was 26 months (range 18-59) 4 remain on therapy, 15 discontinued for progression, 3 discontinued for toxicity, 1 remains off therapy after CR and 1 discontinued following resection of metastasis. Landmark PFS analysis was performed at 18 months: median PFS was 25 months (95% CI, 11-51 mos); median OS was 38 mos (95% CI 25-51). Grade 3 adverse events after 18 mos of sunitinib included diarrhea (29%), fatigue (17%), hand-foot syndrome (21%); unique late toxicities were not observed. Logistic regression analysis from the 139 pts identified bone metastasis, lung metastasis and ≥2 metastatic sites as adverse prognostic factors for long-term response (Table). Conclusions: Sunitinib achieves long-term response in a subset of pts with mRCC. Prolonged treatment was relatively well tolerated without unique late toxicities. Lack of bone metastasis or lung metastases and one metastatic site may predict long-term response. All Long-term responders Univariate logistic analysis (yes vs. no) (N=139) (N=24) Odds ratio (95% CI) p Sites of disease Bone 38 (27%) 3 (13%) 0.33 (0.09, 1.17) 0.08 Lung 97 (70%) 13 (54%) 0.44 (0.18, 1.08) 0.07 Liver 30 (22%) 4 (17%) 0.69 (0.22, 2.18) 0.52 ≥2 metastatic sites 101 (73%) 14 (58%) 0.45 (0.18, 1.13) 0.09 Prior treatment 72 (52%) 16 (67%) 1.91 (0.75, 4.85) 0.17 Clear cell histology 117 (84%) 21 (88%) 1.39 (0.38, 5.11) 0.62 MSKCC risk group Favorable 72 (52%) 15 (63%) 1.70 (0.69, 4.19) 0.25 Intermediate/poor 67 (48%) 9 (37.5%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Genentech, Pfizer
Abstract 4731: Therapeutic targeting of RNA splicing through inhibition of protein arginine methylation
Authors: Jia Yi Fong, Diana Low, Luca Pignata, Kimihito Cojin Kawabata, Stanley CW Lee, Cheryl Koh, Daniele Musiani, Enrico Massignani, Cheng Mun Wun, Pierre-Alexis V. Goy, Yudao Shen, Heike Wollmann, Florence PH Gay, Genna Luciani, Dalia Barsyte, Jian Jin, Ari M. Melnick, Tiziana Bonaldi, Omar Abdel-Wahab, Ernesto Guccione
Journal: Cancer Research (2019)

Abstract Mutations in RNA splicing factors commonly occur in myeloid leukemia and solid tumors. These mutations occur in a heterozygous manner and confer dependency on the wild-type allele. Studies have shown that splicing factor mutant cancers are vulnerable to further perturbation of splicing, by pharmacological intervention that directly targets core splicing factors. Our project identifies the use of PRMT inhibitors, as plausible alternative therapeutic strategy to treat spliceosomal mutant leukemia. The data show that splicing factor mutant leukemia exhibit greater sensitivity to the use of inhibitors against Type I PRMTs and PRMT5, in comparison to their wild-type counterparts. As the need for new therapeutic strategies in cancer treatment increases, this study identifies PRMT inhibitors as a potential therapeutic intervention against cancers with splicing factor mutations. Citation Format: Jia Yi Fong, Diana Low, Luca Pignata, Kimihito Cojin Kawabata, Stanley CW Lee, Cheryl Koh, Daniele Musiani, Enrico Massignani, Cheng Mun Wun, Pierre-Alexis V. Goy, Yudao Shen, Heike Wollmann, Florence PH Gay, Genna Luciani, Dalia Barsyte, Jian Jin, Ari M. Melnick, Tiziana Bonaldi, Omar Abdel-Wahab, Ernesto Guccione. Therapeutic targeting of RNA splicing through inhibition of protein arginine methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4731.
Tumor-Suppressor Genes: Cardinal Factors in Inherited Predisposition to Human Cancers
Authors: H. John Evans, Jane Prosser
Journal: Environmental Health Perspectives (1992)

A predisposition to the development of certain specific and familial cancers is associated with the inheritance of a single mutated gene. In the best-characterized cases, this primary mutation is a loss of function mutation consistent with viability but resulting in neoplastic change consequent to the acquisition of a second somatic mutation at the same locus. Such genes are referred to as tumor-suppressor genes. Classical examples are the Rb-1 gene associated with the development of retinoblastoma and the p53 gene, which is associated with a wider range of neoplasms, including breast cancer. Other tumor-suppressor genes have been isolated which are associated with Wilms' tumor, neurofibromatosis, and inherited and sporadic forms of colorectal cancer. Some of these genes appear to act as negative regulators of mitotic cycle genes, and others may have different properties. The nature of these genes is discussed, as is the evidence for the involvement of tumor-suppressor genes in other inherited, and sporadic, forms of cancer. Some recent data on the Wilms' tumor gene, WT1, and on the involvement of the p53 gene in breast cancer are presented, and the importance of genomic imprinting in contributing to the excess of suppressor gene mutations in chromosomes of paternal origin is considered.
Dysplasia in Crohn's disease may indicate cancer
Journal: JAMA (1981)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality Therapy—The Yale Experience
Authors: Alan J. Koletsky, Joseph R. Bertino, Leonard R. Farber, Leonard R. Prosnitz, Daniel S. Kapp, Diana Fischer, Carol S. Portlock
Journal: Journal of Clinical Oncology (1986)

In the article by Koletsky et al "Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality Therapy-The Yale Experience" (Journal of Clinical Oncology 4:311-317, 1986), an error was made in the footnote on page 311 which described the composition of MVVPP. The corrected footnote appears below. *MVVPP = nitrogen mustard (0.4 mg/kg on day 1 of cycle); vinblastine (6 mg/m2 on days 22, 29, and 36); vincristine (1.4 mg/m2, 2 mg maximum dose, on days 1, 8, and 15); procarbazine (100 mg/d on days 22 through 42); prednisone (40 mg/m2 on days 1 through 15 for cycles 1, 3, and 5 only).
Proplatelet Formation Is Regulated by the Rho/Rock Pathway.
Authors: Yunhua Chang, Frederic Aurade, Frederic Larbret, Jean Pierre Le Couedic, Laurence Momeux, Yan Yan Zhang, Jerome Larghero, Fawzia Louache, Jacques Bertoglio, Elisabeth Cramer, William Vainchenker, Najet Debili
Journal: Blood (2005)
Concomitant CYP2D6 inhibitor use and tamoxifen adherence in early-stage breast cancer: A pharmacoepidemiologic study
Authors: V. Dezentje, N. J. Van Blijderveen, H. Gelderblom, H. Putter, M. P. Van Herk-Sukel, M. K. Casparie, A. C. Egberts, J. W. Nortier, H. J. Guchelaar
Journal: Journal of Clinical Oncology (2009)

CRA509 Background: The use of cytochrome P450 2D6 inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as the commonly prescribed selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in breast cancer. The objectives were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event free time (EFT). Methods: Data were used from PHARMO, a pharmacy database, PALGA, a nationwide pathology database and the Dutch Medical Register in the Netherlands. Breast cancer patients who were treated with tamoxifen as adjuvant therapy between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for the CYP2D6 inhibitor exposure was used. Results: 1,990 breast cancer patients using tamoxifen were included, among whom 215 (10.8%) used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed. Poor tamoxifen adherence was associated with lower EFT. Conclusions: This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen. However, this study shows for the first time that poor tamoxifen adherence is associated with lower EFT. No significant financial relationships to disclose.
Innovative rehabilitation programs get 'them ol' bones' walking around again
Authors: B. Merz
Journal: JAMA (1988)

TREATING musculoskeletal diseases in the aged is one thing. Rehabilitating elderly patients is another. According to participants at a recent national multidisciplinary conference, the latter is often a greater challenge than the former. At the fifth annual seminar titled "Them Ol' Bones," sponsored by St Luke's Medical Center in Phoenix, specialists in orthopedics, rheumatic diseases, physiatrics, and rehabilitation nursing offered a number of suggestions designed not so much to add years to the patients' lives as to add life to their years. Participants generally agreed that the overall goal of rehabilitation defined by Stanley Wainapel, MD, is to restore the patient to the maximum level of his or her physical, mental, social, and vocational abilities. The hard part is determining these abilities in the individual patient, says Wainapel, who is assistant director of physical medicine and rehabilitation, St Luke's Hospital, New York City. He cites statistics from studies showing that
Pembrolizumab for patients with previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: Phase 2 KEYNOTE-180 study.
Authors: Manish A. Shah, Takashi Kojima, Peter C. Enzinger, Daniel Hochhauser, Judith Raimbourg, Antoine Hollebecque, Florian Lordick, Sung-Bae Kim, Masahiro Tajika, Heung Tae Kim, Albert Craig Lockhart, Hendrik-Tobias Arkenau, Farid El Hajbi, Mukul Gupta, Per Pfeiffer, Qi Liu, Jared Lunceford, S. Peter Kang, Pooja Bhagia, Ken Kato
Journal: Journal of Clinical Oncology (2018)

4049 Background: Effective therapy for patients (pts) with metastatic esophageal cancer progressing after at least 2 lines of prior therapy is an unmet need. The phase 2, open-label, KEYNOTE-180 (NCT02559687) study evaluated the activity of pembrolizumab (pembro) in pts with previously treated, advanced/metastatic adenocarcinoma (EAC) or squamous cell carcinoma (ESCC) of the esophagus or Siewert type 1 adenocarcinoma of the gastroesophageal junction. Methods: Eligible pts with metastatic esophageal cancer, ≥2 prior lines of therapy, and tumor samples evaluable for biomarker expression, received pembro 200 mg Q3W for up to 2 years, or until disease progression, unacceptable toxicity, or withdrawal. Tumor response was assessed Q9W (RECISTv1.1, central review). PD-L1+ pts had combined positive score ≥10 using IHC (22C3 antibody). Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, DOR, PFS, and OS. Results: Of 121 pts enrolled (Jan 12, 2016 to March 21, 2017), 100 (83%) were male, median age was 65 years (range 33-87), 63 (52%) had ESCC, and 58 (48%) had PD-L1+ tumors. As of September 18, 2017, median duration of follow-up was 5.8 mo (range, 0.2-18.3). ORR (CR+PR) was 10% (95% CI, 5%-17%); 12 (10%) pts had PR, 25 (21%) SD). Median DOR was not reached ([NR] range, 1.9+ mo to 14.4+ mo), and median PFS was 2 mo (95% CI, 1.9-2.1) with 6-mo PFS rate of 16% (95% CI, 10-23). Median OS was 5.8 mo (95% CI, 4.5-7.2) with 12-mo OS rate of 28% (95% CI, 20-37). In ESCC, ORR was 14% (95% CI, 7-25), and in EAC ORR was 5% (95% CI, 1-14). In PD-L1+ pts, ORR was 14% (95% CI, 6-25) and in PD-L1- pts ORR was 6% (95% CI, 2-16). Overall, 15 (12%) pts had treatment-related grade 3-5 AEs. Five (4%) pts discontinued due to a treatment-related AE. There was one treatment-related death from pneumonitis. Conclusions: Pembro provided durable clinical benefit with manageable safety for pts with heavily pretreated esophageal cancer. A phase 3 study, KEYNOTE-181 (NCT02564263), to evaluate the activity of pembro versus standard therapy in pts with metastatic esophageal carcinoma progressing after first-line therapy is ongoing. Clinical trial information: NCT02559687.
Lead Toxicity and Nutritional Deficiencies
Authors: Orville A. Levander
Journal: Environmental Health Perspectives (1979)

Under appropriate conditions, deficiencies of certain minerals and vitamins as well as high intakes of dietary fat increase the toxicity of a given dose of lead in experimental animals. The severity of lead poisoning can also be increased by the consumption of either deficient or excessive levels of protein. Mineral deficiencies appear to have some of the most profound effects on lead toxicity, since the consequences of plumbism can be exaggerated by feeding diets low in calcium, phosphorus, iron, zinc, and in some cases, copper. Evidence for an antagonism between lead and nutritional levels of selenium is inconclusive. Vitamin E deficiency and lead poisoning interact to produce an anemia in rats that is more severe than that caused by either treatment alone. Lead apparently exerts a pro-oxidant stress on the red cell, thereby causing its accelerated destruction. One of the biochemical mechanisms of lead poisoning may be the disruption of normal membrane architecture, thereby leading to peroxidative damage. Epidemiological surveys have suggested a negative correlation between the poor nutritional status of children with regard to calcium and the concentration of lead in blood. Other examples of potential interactions of mineral status and lead poisoning in humans include the hypothesized hazards of soft water to public health in areas with lead plumbing and the possible role of mineral deficiencies in the etiology of pica. Experimental studies have shown that in some situations combined nutritional deficiencies can have an additive effect in potentiating lead toxicity.